AU2012359165A1 - Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol - Google Patents
Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol Download PDFInfo
- Publication number
- AU2012359165A1 AU2012359165A1 AU2012359165A AU2012359165A AU2012359165A1 AU 2012359165 A1 AU2012359165 A1 AU 2012359165A1 AU 2012359165 A AU2012359165 A AU 2012359165A AU 2012359165 A AU2012359165 A AU 2012359165A AU 2012359165 A1 AU2012359165 A1 AU 2012359165A1
- Authority
- AU
- Australia
- Prior art keywords
- constituent
- disease
- lysosomal
- ambroxol
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 title claims description 305
- 229960005174 ambroxol Drugs 0.000 title claims description 217
- 150000001875 compounds Chemical class 0.000 title claims description 193
- 102000004190 Enzymes Human genes 0.000 title claims description 83
- 108090000790 Enzymes Proteins 0.000 title claims description 83
- 230000002132 lysosomal effect Effects 0.000 title claims description 39
- 239000000470 constituent Substances 0.000 claims description 821
- 108010045758 lysosomal proteins Proteins 0.000 claims description 555
- 230000000694 effects Effects 0.000 claims description 333
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 323
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 312
- 201000010099 disease Diseases 0.000 claims description 311
- 150000003839 salts Chemical class 0.000 claims description 306
- 230000002829 reductive effect Effects 0.000 claims description 274
- 208000015439 Lysosomal storage disease Diseases 0.000 claims description 202
- 238000011282 treatment Methods 0.000 claims description 147
- 230000002265 prevention Effects 0.000 claims description 96
- 208000024720 Fabry Disease Diseases 0.000 claims description 92
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims description 83
- 229940088598 enzyme Drugs 0.000 claims description 82
- 108090000623 proteins and genes Proteins 0.000 claims description 81
- 208000008955 Mucolipidoses Diseases 0.000 claims description 74
- 102000004169 proteins and genes Human genes 0.000 claims description 74
- 230000002950 deficient Effects 0.000 claims description 69
- 201000004502 glycogen storage disease II Diseases 0.000 claims description 68
- 230000035772 mutation Effects 0.000 claims description 66
- OJGDCBLYJGHCIH-UHFFFAOYSA-N bromhexine Chemical compound C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N OJGDCBLYJGHCIH-UHFFFAOYSA-N 0.000 claims description 65
- 229960003870 bromhexine Drugs 0.000 claims description 65
- 208000018737 Parkinson disease Diseases 0.000 claims description 64
- 238000006731 degradation reaction Methods 0.000 claims description 64
- 238000000034 method Methods 0.000 claims description 64
- 230000015556 catabolic process Effects 0.000 claims description 63
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 claims description 61
- 201000008892 GM1 Gangliosidosis Diseases 0.000 claims description 56
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 claims description 55
- 230000000144 pharmacologic effect Effects 0.000 claims description 55
- 201000008049 fucosidosis Diseases 0.000 claims description 49
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims description 46
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 claims description 45
- 208000028226 Krabbe disease Diseases 0.000 claims description 45
- 206010072927 Mucolipidosis type I Diseases 0.000 claims description 45
- 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 claims description 43
- 208000025919 mucopolysaccharidosis type 7 Diseases 0.000 claims description 42
- LXBIFEVIBLOUGU-UHFFFAOYSA-N 1-deoxynojirimycin Chemical compound OCC1NCC(O)C(O)C1O LXBIFEVIBLOUGU-UHFFFAOYSA-N 0.000 claims description 40
- 201000008977 glycoproteinosis Diseases 0.000 claims description 40
- 208000011985 sialidosis Diseases 0.000 claims description 40
- 208000022292 Tay-Sachs disease Diseases 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 38
- LXBIFEVIBLOUGU-JGWLITMVSA-N duvoglustat Chemical compound OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-JGWLITMVSA-N 0.000 claims description 37
- 208000021811 Sandhoff disease Diseases 0.000 claims description 36
- 230000032258 transport Effects 0.000 claims description 34
- 235000000346 sugar Nutrition 0.000 claims description 32
- 230000001965 increasing effect Effects 0.000 claims description 31
- DRHXTSWSUAJOJZ-FMDGEEDCSA-N (3ar,5r,6s,7r,7ar)-5-(hydroxymethyl)-2-methyl-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(C)=N[C@H]2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]2O DRHXTSWSUAJOJZ-FMDGEEDCSA-N 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 27
- IHKWXDCSAKJQKM-SRQGCSHVSA-N n-[(1s,6s,7r,8r,8ar)-1,7,8-trihydroxy-1,2,3,5,6,7,8,8a-octahydroindolizin-6-yl]acetamide Chemical compound O[C@H]1[C@H](O)[C@@H](NC(=O)C)CN2CC[C@H](O)[C@@H]21 IHKWXDCSAKJQKM-SRQGCSHVSA-N 0.000 claims description 27
- 101710124976 Beta-hexosaminidase A Proteins 0.000 claims description 26
- 101710124978 Beta-hexosaminidase B Proteins 0.000 claims description 26
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 claims description 26
- 230000007812 deficiency Effects 0.000 claims description 26
- 102000035160 transmembrane proteins Human genes 0.000 claims description 26
- 108091005703 transmembrane proteins Proteins 0.000 claims description 26
- 208000009796 Gangliosidoses Diseases 0.000 claims description 24
- 201000006440 gangliosidosis Diseases 0.000 claims description 24
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 claims description 22
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 22
- UPZUHYMBTUUPML-QPSCCSFWSA-N (1s,2s,3s,6r)-4-(hydroxymethyl)-6-(octylamino)cyclohex-4-ene-1,2,3-triol Chemical compound CCCCCCCCN[C@@H]1C=C(CO)[C@H](O)[C@H](O)[C@H]1O UPZUHYMBTUUPML-QPSCCSFWSA-N 0.000 claims description 21
- HLXHCNWEVQNNKA-UHFFFAOYSA-N 5-methoxy-2,3-dihydro-1h-inden-2-amine Chemical compound COC1=CC=C2CC(N)CC2=C1 HLXHCNWEVQNNKA-UHFFFAOYSA-N 0.000 claims description 21
- UQRORFVVSGFNRO-UTINFBMNSA-N miglustat Chemical compound CCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO UQRORFVVSGFNRO-UTINFBMNSA-N 0.000 claims description 21
- 208000001905 GM2 Gangliosidoses Diseases 0.000 claims description 19
- 201000008905 GM2 gangliosidosis Diseases 0.000 claims description 19
- 101001045440 Homo sapiens Beta-hexosaminidase subunit alpha Proteins 0.000 claims description 19
- 239000002552 dosage form Substances 0.000 claims description 19
- 230000002255 enzymatic effect Effects 0.000 claims description 19
- 150000002632 lipids Chemical class 0.000 claims description 19
- 150000003408 sphingolipids Chemical class 0.000 claims description 18
- FTSCEGKYKXESFF-LXTVHRRPSA-N N-nonyldeoxynojirimycin Chemical compound CCCCCCCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO FTSCEGKYKXESFF-LXTVHRRPSA-N 0.000 claims description 17
- 108010017544 Glucosylceramidase Proteins 0.000 claims description 16
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 claims description 16
- 108010028144 alpha-Glucosidases Proteins 0.000 claims description 16
- 208000011518 Danon disease Diseases 0.000 claims description 15
- 229920002527 Glycogen Polymers 0.000 claims description 15
- 208000001500 Glycogen Storage Disease Type IIb Diseases 0.000 claims description 15
- 208000035148 Glycogen storage disease due to LAMP-2 deficiency Diseases 0.000 claims description 15
- QPYJXFZUIJOGNX-HSUXUTPPSA-N afegostat Chemical compound OC[C@H]1CNC[C@@H](O)[C@@H]1O QPYJXFZUIJOGNX-HSUXUTPPSA-N 0.000 claims description 15
- 229930182830 galactose Natural products 0.000 claims description 15
- 229940096919 glycogen Drugs 0.000 claims description 15
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 claims description 15
- JDVVGAQPNNXQDW-WCMLQCRESA-N Castanospermine Natural products O[C@H]1[C@@H](O)[C@H]2[C@@H](O)CCN2C[C@H]1O JDVVGAQPNNXQDW-WCMLQCRESA-N 0.000 claims description 14
- JDVVGAQPNNXQDW-TVNFTVLESA-N Castinospermine Chemical compound C1[C@H](O)[C@@H](O)[C@H](O)[C@H]2[C@@H](O)CCN21 JDVVGAQPNNXQDW-TVNFTVLESA-N 0.000 claims description 14
- 206010072928 Mucolipidosis type II Diseases 0.000 claims description 14
- 208000034012 Acid sphingomyelinase deficiency Diseases 0.000 claims description 13
- -1 N-octyl isofagomine Chemical compound 0.000 claims description 13
- 108010005774 beta-Galactosidase Proteins 0.000 claims description 13
- 230000007547 defect Effects 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 230000004060 metabolic process Effects 0.000 claims description 13
- LXBIFEVIBLOUGU-DPYQTVNSSA-N migalastat Chemical group OC[C@H]1NC[C@H](O)[C@@H](O)[C@H]1O LXBIFEVIBLOUGU-DPYQTVNSSA-N 0.000 claims description 13
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 claims description 13
- RLJOYSOPEJBIAA-UHFFFAOYSA-N 2-nitro-2,3-dihydroinden-1-one Chemical compound C1=CC=C2C(=O)C([N+](=O)[O-])CC2=C1 RLJOYSOPEJBIAA-UHFFFAOYSA-N 0.000 claims description 12
- 102000003886 Glycoproteins Human genes 0.000 claims description 12
- 108090000288 Glycoproteins Proteins 0.000 claims description 12
- 102000004157 Hydrolases Human genes 0.000 claims description 12
- 108090000604 Hydrolases Proteins 0.000 claims description 12
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 12
- 229950007469 migalastat Drugs 0.000 claims description 12
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- KNSGUARWFVOEEB-UHFFFAOYSA-N pyrrolo[3,4-d]pyridazin-4-one Chemical compound O=C1N=NC=C2C=NC=C12 KNSGUARWFVOEEB-UHFFFAOYSA-N 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 102100028496 Galactocerebrosidase Human genes 0.000 claims description 11
- 108010042681 Galactosylceramidase Proteins 0.000 claims description 11
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 11
- 208000000149 Multiple Sulfatase Deficiency Disease Diseases 0.000 claims description 11
- 208000035032 Multiple sulfatase deficiency Diseases 0.000 claims description 11
- 102000005348 Neuraminidase Human genes 0.000 claims description 11
- 108010006232 Neuraminidase Proteins 0.000 claims description 11
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 claims description 11
- 108010030291 alpha-Galactosidase Proteins 0.000 claims description 11
- 235000012000 cholesterol Nutrition 0.000 claims description 11
- GBRAQQUMMCVTAV-LXGUWJNJSA-N n-[(3s,4r,5r,6r)-4,5-dihydroxy-6-(hydroxymethyl)piperidin-3-yl]acetamide Chemical compound CC(=O)N[C@H]1CN[C@H](CO)[C@@H](O)[C@@H]1O GBRAQQUMMCVTAV-LXGUWJNJSA-N 0.000 claims description 11
- UPZUHYMBTUUPML-KBXIAJHMSA-N (1s,2s,3r,6r)-4-(hydroxymethyl)-6-(octylamino)cyclohex-4-ene-1,2,3-triol Chemical compound CCCCCCCCN[C@@H]1C=C(CO)[C@@H](O)[C@H](O)[C@H]1O UPZUHYMBTUUPML-KBXIAJHMSA-N 0.000 claims description 10
- YZPAVTVEJWCWQB-UHFFFAOYSA-N Calystegine Chemical compound C1C(O)C(O)C2(O)CCC1C2N YZPAVTVEJWCWQB-UHFFFAOYSA-N 0.000 claims description 10
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 claims description 10
- 208000000828 Sialic Acid Storage Disease Diseases 0.000 claims description 10
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 claims description 10
- 150000001840 cholesterol esters Chemical class 0.000 claims description 10
- 150000004676 glycans Chemical class 0.000 claims description 10
- 201000010108 pycnodysostosis Diseases 0.000 claims description 10
- XOCBOVUINUHZJA-JRTVQGFMSA-N Calystegin A3 Natural products O[C@H]1[C@@H](O)C[C@@H]2N[C@@]1(O)CC2 XOCBOVUINUHZJA-JRTVQGFMSA-N 0.000 claims description 9
- 208000001948 Farber Lipogranulomatosis Diseases 0.000 claims description 9
- 208000033149 Farber disease Diseases 0.000 claims description 9
- 206010072929 Mucolipidosis type III Diseases 0.000 claims description 9
- 102000012086 alpha-L-Fucosidase Human genes 0.000 claims description 9
- 108010061314 alpha-L-Fucosidase Proteins 0.000 claims description 9
- XOCBOVUINUHZJA-UHFFFAOYSA-N calystegine A3 Natural products OC1C(O)CC2CCC1(O)N2 XOCBOVUINUHZJA-UHFFFAOYSA-N 0.000 claims description 9
- FXFBVZOJVHCEDO-IBISWUOJSA-N (1s,2r,3s,4r,5s)-8-azabicyclo[3.2.1]octane-1,2,3,4-tetrol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H]2CC[C@]1(O)N2 FXFBVZOJVHCEDO-IBISWUOJSA-N 0.000 claims description 8
- FXFBVZOJVHCEDO-AZEWMMITSA-N Calystegin B2 Natural products O[C@@H]1[C@H](O)[C@@]2(O)N[C@H]([C@@H]1O)CC2 FXFBVZOJVHCEDO-AZEWMMITSA-N 0.000 claims description 8
- 102000053187 Glucuronidase Human genes 0.000 claims description 8
- 108010060309 Glucuronidase Proteins 0.000 claims description 8
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 claims description 8
- FXFBVZOJVHCEDO-UHFFFAOYSA-N calystegine B2 Natural products OC1C(O)C(O)C2CCC1(O)N2 FXFBVZOJVHCEDO-UHFFFAOYSA-N 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- RMCNETIHECSPMZ-NGQZWQHPSA-N (3s,5r)-piperidine-3,4,5-triol Chemical compound O[C@H]1CNC[C@@H](O)C1O RMCNETIHECSPMZ-NGQZWQHPSA-N 0.000 claims description 7
- YRBKDBZXOAEMOT-UHFFFAOYSA-N 6-deoxy-DMDP Natural products CC1NC(CO)C(O)C1O YRBKDBZXOAEMOT-UHFFFAOYSA-N 0.000 claims description 7
- 206010011777 Cystinosis Diseases 0.000 claims description 7
- 208000017462 Galactosialidosis Diseases 0.000 claims description 7
- 102000002464 Galactosidases Human genes 0.000 claims description 7
- 108010093031 Galactosidases Proteins 0.000 claims description 7
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims description 7
- 108010044965 UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase Proteins 0.000 claims description 7
- QPYJXFZUIJOGNX-PBXRRBTRSA-N (3r,4s,5r)-5-(hydroxymethyl)piperidine-3,4-diol Chemical compound OC[C@H]1CNC[C@@H](O)[C@H]1O QPYJXFZUIJOGNX-PBXRRBTRSA-N 0.000 claims description 6
- 206010068220 Aspartylglucosaminuria Diseases 0.000 claims description 6
- 108700037017 Hyaluronidase Deficiency Proteins 0.000 claims description 6
- 208000005503 Hyaluronidase deficiency Diseases 0.000 claims description 6
- 208000025820 Sanfilippo syndrome type B Diseases 0.000 claims description 6
- 208000025802 Sanfilippo syndrome type C Diseases 0.000 claims description 6
- 208000025804 Sanfilippo syndrome type D Diseases 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 6
- 201000002273 mucopolysaccharidosis II Diseases 0.000 claims description 6
- 208000036709 mucopolysaccharidosis type 3B Diseases 0.000 claims description 6
- 208000036707 mucopolysaccharidosis type 3C Diseases 0.000 claims description 6
- 208000036725 mucopolysaccharidosis type 3D Diseases 0.000 claims description 6
- 208000012227 mucopolysaccharidosis type IIIB Diseases 0.000 claims description 6
- 208000012224 mucopolysaccharidosis type IIIC Diseases 0.000 claims description 6
- 208000027333 mucopolysaccharidosis type IIID Diseases 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- AXNKITZDVRGIRT-XDQVBPFNSA-N (1R,2S,3S,4S)-1,4-bis(hydroxymethyl)-6-octyl-5-oxa-6-azabicyclo[2.1.1]hexane-2,3-diol Chemical compound C(CCCCCCC)N1[C@]2(CO)[C@@H](O)[C@H](O)[C@]1(O2)CO AXNKITZDVRGIRT-XDQVBPFNSA-N 0.000 claims description 5
- XOCBOVUINUHZJA-MVIOUDGNSA-N (1r,3r,4s,5r)-8-azabicyclo[3.2.1]octane-3,4,5-triol Chemical compound O[C@H]1[C@H](O)C[C@H]2CC[C@]1(O)N2 XOCBOVUINUHZJA-MVIOUDGNSA-N 0.000 claims description 5
- 102100031317 Alpha-N-acetylgalactosaminidase Human genes 0.000 claims description 5
- 102100034561 Alpha-N-acetylglucosaminidase Human genes 0.000 claims description 5
- 102100022146 Arylsulfatase A Human genes 0.000 claims description 5
- 102100031491 Arylsulfatase B Human genes 0.000 claims description 5
- 108010036867 Cerebroside-Sulfatase Proteins 0.000 claims description 5
- 208000020322 Gaucher disease type I Diseases 0.000 claims description 5
- 208000020916 Gaucher disease type II Diseases 0.000 claims description 5
- 208000028735 Gaucher disease type III Diseases 0.000 claims description 5
- 208000015178 Hurler syndrome Diseases 0.000 claims description 5
- 208000015204 Hurler-Scheie syndrome Diseases 0.000 claims description 5
- 102000004882 Lipase Human genes 0.000 claims description 5
- 108090001060 Lipase Proteins 0.000 claims description 5
- 102000009565 Lysosomal-Associated Membrane Protein 2 Human genes 0.000 claims description 5
- 108010009491 Lysosomal-Associated Membrane Protein 2 Proteins 0.000 claims description 5
- 208000027933 Mannosidase Deficiency disease Diseases 0.000 claims description 5
- 206010072930 Mucolipidosis type IV Diseases 0.000 claims description 5
- 102100026502 Mucolipin-1 Human genes 0.000 claims description 5
- 108010027520 N-Acetylgalactosamine-4-Sulfatase Proteins 0.000 claims description 5
- BGMYHTUCJVZIRP-UHFFFAOYSA-N Nojirimycin Natural products OCC1NC(O)C(O)C(O)C1O BGMYHTUCJVZIRP-UHFFFAOYSA-N 0.000 claims description 5
- 208000013608 Salla disease Diseases 0.000 claims description 5
- 208000025816 Sanfilippo syndrome type A Diseases 0.000 claims description 5
- 201000002883 Scheie syndrome Diseases 0.000 claims description 5
- 102000011971 Sphingomyelin Phosphodiesterase Human genes 0.000 claims description 5
- 108010015684 alpha-N-Acetylgalactosaminidase Proteins 0.000 claims description 5
- 108010009380 alpha-N-acetyl-D-glucosaminidase Proteins 0.000 claims description 5
- 208000036710 mucopolysaccharidosis type 3A Diseases 0.000 claims description 5
- 208000012226 mucopolysaccharidosis type IIIA Diseases 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- BQFFLYRIKODYEN-CXNFULCWSA-N (1s,3r,4s,5r,7r)-8-azabicyclo[3.2.1]octane-3,4,5,7-tetrol Chemical compound N1[C@@H]2[C@H](O)C[C@@]1(O)[C@@H](O)[C@H](O)C2 BQFFLYRIKODYEN-CXNFULCWSA-N 0.000 claims description 4
- ZEWFPWKROPWRKE-CQOGJGKDSA-N (2r,3r,4r,5r,6s)-2-(hydroxymethyl)-6-methylpiperidine-3,4,5-triol Chemical compound C[C@@H]1N[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O ZEWFPWKROPWRKE-CQOGJGKDSA-N 0.000 claims description 4
- YRBKDBZXOAEMOT-ARQDHWQXSA-N (2r,3r,4s,5r)-2-(hydroxymethyl)-5-methylpyrrolidine-3,4-diol Chemical compound C[C@H]1N[C@H](CO)[C@@H](O)[C@H]1O YRBKDBZXOAEMOT-ARQDHWQXSA-N 0.000 claims description 4
- YRBKDBZXOAEMOT-DPYQTVNSSA-N (2s,3r,4s,5r)-2-(hydroxymethyl)-5-methylpyrrolidine-3,4-diol Chemical compound C[C@H]1N[C@@H](CO)[C@@H](O)[C@H]1O YRBKDBZXOAEMOT-DPYQTVNSSA-N 0.000 claims description 4
- QNVKOSLOVOTXKF-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 QNVKOSLOVOTXKF-UHFFFAOYSA-N 0.000 claims description 4
- 102000006772 Acid Ceramidase Human genes 0.000 claims description 4
- 108020005296 Acid Ceramidase Proteins 0.000 claims description 4
- 208000028568 Free sialic acid storage disease Diseases 0.000 claims description 4
- BLOFGONIVNXZME-UHFFFAOYSA-N Mannostatin A Natural products CSC1C(N)C(O)C(O)C1O BLOFGONIVNXZME-UHFFFAOYSA-N 0.000 claims description 4
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims description 4
- 108091000080 Phosphotransferase Proteins 0.000 claims description 4
- 108091006161 SLC17A5 Proteins 0.000 claims description 4
- 208000017460 Sialidosis type 2 Diseases 0.000 claims description 4
- 102000005262 Sulfatase Human genes 0.000 claims description 4
- DCVWZPYTNWZZIM-UHFFFAOYSA-N alpha-7-deoxyhomonojirimycin Natural products CC1NC(CO)C(O)CC1O DCVWZPYTNWZZIM-UHFFFAOYSA-N 0.000 claims description 4
- 229960000985 ambroxol hydrochloride Drugs 0.000 claims description 4
- 229960002335 bromhexine hydrochloride Drugs 0.000 claims description 4
- BQFFLYRIKODYEN-UHFFFAOYSA-N calystegine B1 Natural products N1C2C(O)CC1(O)C(O)C(O)C2 BQFFLYRIKODYEN-UHFFFAOYSA-N 0.000 claims description 4
- YRSGDLIATOURQO-UHFFFAOYSA-N ethyl 4-acetyl-5-oxohexanoate Chemical group CCOC(=O)CCC(C(C)=O)C(C)=O YRSGDLIATOURQO-UHFFFAOYSA-N 0.000 claims description 4
- BLOFGONIVNXZME-YDMGZANHSA-N mannostatin A Chemical compound CS[C@@H]1[C@@H](N)[C@@H](O)[C@@H](O)[C@H]1O BLOFGONIVNXZME-YDMGZANHSA-N 0.000 claims description 4
- 102000020233 phosphotransferase Human genes 0.000 claims description 4
- 108060007951 sulfatase Proteins 0.000 claims description 4
- FXUAIOOAOAVCGD-UHFFFAOYSA-N swainsonine Natural products C1CCC(O)C2C(O)C(O)CN21 FXUAIOOAOAVCGD-UHFFFAOYSA-N 0.000 claims description 4
- FXUAIOOAOAVCGD-FKSUSPILSA-N swainsonine Chemical compound C1CC[C@H](O)[C@H]2[C@H](O)[C@H](O)CN21 FXUAIOOAOAVCGD-FKSUSPILSA-N 0.000 claims description 4
- 229960005566 swainsonine Drugs 0.000 claims description 4
- 239000003826 tablet Substances 0.000 claims description 4
- CLVUFWXGNIFGNC-QTSLKERKSA-N (2r,3s,5r,6r)-2,6-bis(hydroxymethyl)piperidine-3,4,5-triol Chemical compound OC[C@H]1N[C@H](CO)[C@H](O)C(O)[C@@H]1O CLVUFWXGNIFGNC-QTSLKERKSA-N 0.000 claims description 3
- ZSNFEMNRWFDMNU-CVPUBMOQSA-N (2s,3s,4r,5s,6r)-2-butyl-6-(hydroxymethyl)piperidine-3,4,5-triol Chemical group CCCC[C@@H]1N[C@H](CO)[C@H](O)[C@H](O)[C@H]1O ZSNFEMNRWFDMNU-CVPUBMOQSA-N 0.000 claims description 3
- YRBKDBZXOAEMOT-VANKVMQKSA-N (2s,3s,4s,5r)-2-(hydroxymethyl)-5-methylpyrrolidine-3,4-diol Chemical compound C[C@H]1N[C@@H](CO)[C@H](O)[C@H]1O YRBKDBZXOAEMOT-VANKVMQKSA-N 0.000 claims description 3
- 108010053317 Hexosaminidase A Proteins 0.000 claims description 3
- 102000016871 Hexosaminidase A Human genes 0.000 claims description 3
- 101000581402 Homo sapiens Melanin-concentrating hormone receptor 1 Proteins 0.000 claims description 3
- 102000037055 SLC1 Human genes 0.000 claims description 3
- 102000010126 acid sphingomyelin phosphodiesterase activity proteins Human genes 0.000 claims description 3
- 102000005840 alpha-Galactosidase Human genes 0.000 claims description 3
- CLVUFWXGNIFGNC-UHFFFAOYSA-N alpha-homonojirimycin Natural products OCC1NC(CO)C(O)C(O)C1O CLVUFWXGNIFGNC-UHFFFAOYSA-N 0.000 claims description 3
- ZSNFEMNRWFDMNU-UHFFFAOYSA-N beta-1-C-butyl-deoxygalactonojirimycin Natural products CCCCC1NC(CO)C(O)C(O)C1O ZSNFEMNRWFDMNU-UHFFFAOYSA-N 0.000 claims description 3
- CLVUFWXGNIFGNC-OVHBTUCOSA-N chembl501355 Chemical compound OC[C@H]1N[C@H](CO)[C@H](O)[C@@H](O)[C@@H]1O CLVUFWXGNIFGNC-OVHBTUCOSA-N 0.000 claims description 3
- 201000007769 mucolipidosis Diseases 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 208000035374 Chronic visceral acid sphingomyelinase deficiency Diseases 0.000 claims description 2
- 108010053345 Hexosaminidase B Proteins 0.000 claims description 2
- 102000016870 Hexosaminidase B Human genes 0.000 claims description 2
- 208000035343 Infantile neurovisceral acid sphingomyelinase deficiency Diseases 0.000 claims description 2
- 102000001696 Mannosidases Human genes 0.000 claims description 2
- 108010054377 Mannosidases Proteins 0.000 claims description 2
- 201000000794 Niemann-Pick disease type A Diseases 0.000 claims description 2
- 201000000791 Niemann-Pick disease type B Diseases 0.000 claims description 2
- 201000000785 Niemann-Pick disease type C2 Diseases 0.000 claims description 2
- 208000007824 Type A Niemann-Pick Disease Diseases 0.000 claims description 2
- 208000008291 Type B Niemann-Pick Disease Diseases 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 102000004547 Glucosylceramidase Human genes 0.000 claims 3
- 102000005936 beta-Galactosidase Human genes 0.000 claims 3
- GGOJRYWHKVYFQK-XQCVOTFFSA-N (1r,2s,3r,4s,5r,7r)-8-azabicyclo[3.2.1]octane-2,3,4,5,7-pentol Chemical group N1[C@@]2(O)C[C@@H](O)[C@]1([H])[C@H](O)[C@@H](O)[C@@H]2O GGOJRYWHKVYFQK-XQCVOTFFSA-N 0.000 claims 1
- LXBIFEVIBLOUGU-KVTDHHQDSA-N (2r,3r,4r,5r)-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound OC[C@H]1NC[C@@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-KVTDHHQDSA-N 0.000 claims 1
- DUROKJUTAMUPAH-UHFFFAOYSA-N 1-nitro-2,3-dihydro-1h-indene Chemical compound C1=CC=C2C([N+](=O)[O-])CCC2=C1 DUROKJUTAMUPAH-UHFFFAOYSA-N 0.000 claims 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 claims 1
- XPHOBMULWMGEBA-UHFFFAOYSA-N Valienamine Natural products NC1C=C(CO)C(O)C(O)C1O XPHOBMULWMGEBA-UHFFFAOYSA-N 0.000 claims 1
- 102000005421 acetyltransferase Human genes 0.000 claims 1
- 108020002494 acetyltransferase Proteins 0.000 claims 1
- GGOJRYWHKVYFQK-UHFFFAOYSA-N calystegine C1 Natural products N1C2C(O)CC1(O)C(O)C(O)C2O GGOJRYWHKVYFQK-UHFFFAOYSA-N 0.000 claims 1
- VYOCYWDJTQRZLC-KCDKBNATSA-N deoxyfuconojirimycin Chemical compound C[C@@H]1NC[C@@H](O)[C@H](O)[C@@H]1O VYOCYWDJTQRZLC-KCDKBNATSA-N 0.000 claims 1
- XPHOBMULWMGEBA-VZFHVOOUSA-N valienamine Chemical compound N[C@H]1C=C(CO)[C@@H](O)[C@H](O)[C@H]1O XPHOBMULWMGEBA-VZFHVOOUSA-N 0.000 claims 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 69
- 235000018102 proteins Nutrition 0.000 description 65
- 102000005431 Molecular Chaperones Human genes 0.000 description 37
- 206010056893 Mucopolysaccharidosis VII Diseases 0.000 description 37
- 206010028095 Mucopolysaccharidosis IV Diseases 0.000 description 36
- 208000010978 mucopolysaccharidosis type 4 Diseases 0.000 description 36
- 201000008333 alpha-mannosidosis Diseases 0.000 description 34
- 201000006486 beta-mannosidosis Diseases 0.000 description 33
- 208000024891 symptom Diseases 0.000 description 19
- 210000003712 lysosome Anatomy 0.000 description 15
- 230000001868 lysosomic effect Effects 0.000 description 15
- 238000002560 therapeutic procedure Methods 0.000 description 13
- 102100026277 Alpha-galactosidase A Human genes 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 description 11
- 102100026189 Beta-galactosidase Human genes 0.000 description 10
- 108010021466 Mutant Proteins Proteins 0.000 description 10
- 102000008300 Mutant Proteins Human genes 0.000 description 10
- 238000009825 accumulation Methods 0.000 description 10
- 230000002708 enhancing effect Effects 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000004952 protein activity Effects 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 206010019842 Hepatomegaly Diseases 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 7
- 230000006641 stabilisation Effects 0.000 description 7
- 238000011105 stabilization Methods 0.000 description 7
- 101000718525 Homo sapiens Alpha-galactosidase A Proteins 0.000 description 6
- 101000589519 Homo sapiens N-acetyltransferase 8 Proteins 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 235000020664 gamma-linolenic acid Nutrition 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 206010041660 Splenomegaly Diseases 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 208000006029 Cardiomegaly Diseases 0.000 description 4
- 102000004627 Iduronidase Human genes 0.000 description 4
- 108010003381 Iduronidase Proteins 0.000 description 4
- 206010028372 Muscular weakness Diseases 0.000 description 4
- 208000027089 Parkinsonian disease Diseases 0.000 description 4
- 206010034010 Parkinsonism Diseases 0.000 description 4
- 206010044565 Tremor Diseases 0.000 description 4
- 108010070626 acid beta-galactosidase Proteins 0.000 description 4
- 230000002860 competitive effect Effects 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 230000012846 protein folding Effects 0.000 description 4
- 230000008707 rearrangement Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- LXBIFEVIBLOUGU-FSIIMWSLSA-N 1-Deoxymannojirimycin Natural products OC[C@@H]1NC[C@@H](O)[C@H](O)[C@H]1O LXBIFEVIBLOUGU-FSIIMWSLSA-N 0.000 description 3
- 108010059081 Cathepsin A Proteins 0.000 description 3
- 102000005572 Cathepsin A Human genes 0.000 description 3
- 102000004171 Cathepsin K Human genes 0.000 description 3
- 108090000625 Cathepsin K Proteins 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- 208000015872 Gaucher disease Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- 208000016285 Movement disease Diseases 0.000 description 3
- 208000010428 Muscle Weakness Diseases 0.000 description 3
- 208000014060 Niemann-Pick disease Diseases 0.000 description 3
- 206010038687 Respiratory distress Diseases 0.000 description 3
- 102100038413 UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase Human genes 0.000 description 3
- 108010024501 UDPacetylglucosamine-dolichyl-phosphate acetylglucosamine-1-phosphate transferase Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 230000003028 elevating effect Effects 0.000 description 3
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 3
- 238000002641 enzyme replacement therapy Methods 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 208000016361 genetic disease Diseases 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 206010000060 Abdominal distension Diseases 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 206010006100 Bradykinesia Diseases 0.000 description 2
- 102000005927 Cysteine Proteases Human genes 0.000 description 2
- 108010005843 Cysteine Proteases Proteins 0.000 description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
- 206010011878 Deafness Diseases 0.000 description 2
- 206010012559 Developmental delay Diseases 0.000 description 2
- 230000006782 ER associated degradation Effects 0.000 description 2
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- 101001122938 Homo sapiens Lysosomal protective protein Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 208000006083 Hypokinesia Diseases 0.000 description 2
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 2
- 102000003939 Membrane transport proteins Human genes 0.000 description 2
- 108090000301 Membrane transport proteins Proteins 0.000 description 2
- 208000002740 Muscle Rigidity Diseases 0.000 description 2
- 101000989950 Otolemur crassicaudatus Hemoglobin subunit alpha-A Proteins 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 102000019355 Synuclein Human genes 0.000 description 2
- 108050006783 Synuclein Proteins 0.000 description 2
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 231100000895 deafness Toxicity 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 208000016354 hearing loss disease Diseases 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 208000000690 mucopolysaccharidosis VI Diseases 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000003019 respiratory muscle Anatomy 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000007958 sleep Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 230000003319 supportive effect Effects 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 108020005087 unfolded proteins Proteins 0.000 description 2
- ULBPPCHRAVUQMC-MUMXBIPUSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;(3r,4r,5r)-5-(hydroxymethyl)piperidine-3,4-diol Chemical compound OC[C@H]1CNC[C@@H](O)[C@@H]1O.OC(=O)[C@H](O)[C@@H](O)C(O)=O ULBPPCHRAVUQMC-MUMXBIPUSA-N 0.000 description 1
- UQRORFVVSGFNRO-XFWSIPNHSA-N (2r,3s,4r,5s)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol Chemical compound CCCCN1C[C@H](O)[C@@H](O)[C@@H](O)[C@H]1CO UQRORFVVSGFNRO-XFWSIPNHSA-N 0.000 description 1
- GOWMBYUZXIZENX-CAUSLRQDSA-N 1-[(2r,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(hexadecylamino)pyrimidin-2-one Chemical compound O=C1N=C(NCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 GOWMBYUZXIZENX-CAUSLRQDSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- DQTKLICLJUKNCG-UHFFFAOYSA-N A-72363 A-1 Natural products CC(=O)NC1NCC(C(O)=O)C(O)C1O DQTKLICLJUKNCG-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000364 Accessory muscle Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 206010070545 Bacterial translocation Diseases 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 101100080277 Caenorhabditis elegans ncr-1 gene Proteins 0.000 description 1
- 241000238097 Callinectes sapidus Species 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010051093 Cardiopulmonary failure Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 208000001573 Cataplexy Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 230000009946 DNA mutation Effects 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 208000014094 Dystonic disease Diseases 0.000 description 1
- 241000901143 Etia Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108010068561 Fructose-Bisphosphate Aldolase Proteins 0.000 description 1
- 102000001390 Fructose-Bisphosphate Aldolase Human genes 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 206010056696 Gaze palsy Diseases 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000860415 Homo sapiens Galanin peptides Proteins 0.000 description 1
- 101001004953 Homo sapiens Lysosomal acid lipase/cholesteryl ester hydrolase Proteins 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000009066 Hyaluronoglucosaminidase Human genes 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 241000575946 Ione Species 0.000 description 1
- AYRXSINWFIIFAE-SCLMCMATSA-N Isomaltose Natural products OC[C@H]1O[C@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)[C@@H](O)[C@@H](O)[C@@H]1O AYRXSINWFIIFAE-SCLMCMATSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 101710096786 Lysosomal acid alpha-glucosidase Proteins 0.000 description 1
- 102100026001 Lysosomal acid lipase/cholesteryl ester hydrolase Human genes 0.000 description 1
- 102100028524 Lysosomal protective protein Human genes 0.000 description 1
- 206010025391 Macroglossia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 208000002678 Mucopolysaccharidoses Diseases 0.000 description 1
- 208000025915 Mucopolysaccharidosis type 6 Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 208000007379 Muscle Hypotonia Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- WHCJUIFHMJFEFZ-IYWGXSQHSA-N N-Acetylgalactosamine 4-sulfate Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](OS(O)(=O)=O)[C@@H]1O WHCJUIFHMJFEFZ-IYWGXSQHSA-N 0.000 description 1
- GZDWTPRPLBRISA-RZUNNTJFSA-N N-Methylcalystegine B2 Chemical group O[C@@H]1[C@@H](O)[C@H](O)[C@]2(O)CC[C@H]1N2C GZDWTPRPLBRISA-RZUNNTJFSA-N 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 108091006036 N-glycosylated proteins Proteins 0.000 description 1
- GZDWTPRPLBRISA-YOWKYNACSA-N N-methylcalystegine B2 Natural products O[C@H]1[C@H](O)[C@@]2(O)N(C)[C@H]([C@@H]1O)CC2 GZDWTPRPLBRISA-YOWKYNACSA-N 0.000 description 1
- 206010052319 Nasal flaring Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000011644 Neurologic Gait disease Diseases 0.000 description 1
- 208000008457 Neurologic Manifestations Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101100459404 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) npc-1 gene Proteins 0.000 description 1
- 208000010577 Niemann-Pick disease type C Diseases 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- 206010036437 Posturing Diseases 0.000 description 1
- 208000008425 Protein deficiency Diseases 0.000 description 1
- 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 1
- 101000718529 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) Alpha-galactosidase Proteins 0.000 description 1
- 102000040739 Secretory proteins Human genes 0.000 description 1
- 108091058545 Secretory proteins Proteins 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 201000001828 Sly syndrome Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000010346 Sphingolipidoses Diseases 0.000 description 1
- 201000001307 Sphingolipidosis Diseases 0.000 description 1
- 208000026589 Wolman disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- NNISLDGFPWIBDF-MPRBLYSKSA-N alpha-D-Gal-(1->3)-beta-D-Gal-(1->4)-D-GlcNAc Chemical compound O[C@@H]1[C@@H](NC(=O)C)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@@H](CO)O1 NNISLDGFPWIBDF-MPRBLYSKSA-N 0.000 description 1
- 102000019199 alpha-Mannosidase Human genes 0.000 description 1
- 108010012864 alpha-Mannosidase Proteins 0.000 description 1
- 102000003802 alpha-Synuclein Human genes 0.000 description 1
- 108090000185 alpha-Synuclein Proteins 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000010065 bacterial adhesion Effects 0.000 description 1
- 230000007375 bacterial translocation Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 1
- 229960003065 bosentan Drugs 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000006800 cellular catabolic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003748 differential diagnosis Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 201000006517 essential tremor Diseases 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 210000001097 facial muscle Anatomy 0.000 description 1
- 206010016165 failure to thrive Diseases 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 206010019847 hepatosplenomegaly Diseases 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000016245 inborn errors of metabolism Diseases 0.000 description 1
- 238000011850 initial investigation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000013190 lipid storage Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229960001512 miglustat Drugs 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000000337 motor cortex Anatomy 0.000 description 1
- 208000020460 mucolipidosis II alpha/beta Diseases 0.000 description 1
- 208000020468 mucolipidosis III alpha/beta Diseases 0.000 description 1
- 206010028093 mucopolysaccharidosis Diseases 0.000 description 1
- 238000001964 muscle biopsy Methods 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 208000026526 progressive weakness Diseases 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000004461 rapid eye movement Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- DQTKLICLJUKNCG-ZTYPAOSTSA-N siastatin b Chemical compound CC(=O)N[C@H]1NC[C@H](C(O)=O)[C@H](O)[C@@H]1O DQTKLICLJUKNCG-ZTYPAOSTSA-N 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000006829 sphingolipid biosynthesis Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 229940099072 zavesca Drugs 0.000 description 1
- 150000008494 α-glucosides Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/45—Non condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Psychology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2017279780A AU2017279780B2 (en) | 2011-12-22 | 2017-12-22 | Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11010078.1 | 2011-12-22 | ||
| EP11010078 | 2011-12-22 | ||
| PCT/EP2012/005363 WO2013091897A1 (en) | 2011-12-22 | 2012-12-21 | Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2017279780A Division AU2017279780B2 (en) | 2011-12-22 | 2017-12-22 | Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2012359165A1 true AU2012359165A1 (en) | 2014-07-10 |
Family
ID=47559375
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2012359165A Abandoned AU2012359165A1 (en) | 2011-12-22 | 2012-12-21 | Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol |
| AU2017279780A Ceased AU2017279780B2 (en) | 2011-12-22 | 2017-12-22 | Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2017279780A Ceased AU2017279780B2 (en) | 2011-12-22 | 2017-12-22 | Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US20150258081A1 (https=) |
| EP (1) | EP2793872B1 (https=) |
| JP (2) | JP6320931B2 (https=) |
| KR (1) | KR102076585B1 (https=) |
| AU (2) | AU2012359165A1 (https=) |
| BR (1) | BR112014014808A2 (https=) |
| CA (1) | CA2860085A1 (https=) |
| ES (1) | ES2864774T3 (https=) |
| IL (1) | IL233173B (https=) |
| WO (1) | WO2013091897A1 (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9675627B2 (en) * | 2014-04-14 | 2017-06-13 | Amicus Therapeutics, Inc. | Dosing regimens for treating and/or preventing cerebral amyloidoses |
| CN114540327B (zh) | 2014-09-30 | 2026-03-24 | 阿米库斯治疗学公司 | 具有增强的碳水化合物的高强度酸性α-葡糖苷酶 |
| GB201508025D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Fabry disease gene therapy |
| JP6981961B2 (ja) * | 2015-07-30 | 2021-12-17 | ホライズン オルファン エルエルシー | フコシダーゼ阻害剤 |
| KR20250007693A (ko) | 2015-12-30 | 2025-01-14 | 아미쿠스 세라퓨틱스, 인코포레이티드 | 폼페병 치료용의 강화된 산 알파-글루코시다제 |
| KR20190087673A (ko) | 2016-03-22 | 2019-07-24 | 아미쿠스 세라퓨틱스, 인코포레이티드 | Ｇｌａ 유전자에 ｇ9331ａ 돌연변이를 갖는 환자에서 파브리 질병의 치료 방법 |
| CA3019354A1 (en) | 2016-03-30 | 2017-10-05 | Amicus Therapeutics, Inc. | Method for selection of high m6p recombinant proteins |
| AU2017239641A1 (en) | 2016-03-30 | 2018-10-18 | Amicus Therapeutics, Inc. | Formulations comprising recombinant acid alpha-glucosidase |
| US20190254992A1 (en) * | 2016-06-29 | 2019-08-22 | Hadasit Medical Research Services & Development Limited | Combinations of beta-glycolipides and 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol, compositions and uses thereof in the treatment of disorders associated with protein misfolding and protein aggregations |
| WO2018089797A1 (en) * | 2016-11-14 | 2018-05-17 | Mingwu Wang | Formulations for the treatment of ocular surface diseases and related methods |
| CN110573492A (zh) * | 2017-04-25 | 2019-12-13 | 阿米库斯治疗学公司 | 用于预防和/或治疗中枢神经系统退行性失调和/或溶酶体贮积失调的新颖组合物 |
| SMT202300187T1 (it) | 2017-05-15 | 2023-07-20 | Amicus Therapeutics Inc | Alfa-glucosidasi acida umana ricombinante |
| CA3224546C (en) | 2017-05-30 | 2026-02-24 | Amicus Therapeutics, Inc. | Use of migalastat in the treatment of fabry patients |
| US20220184185A1 (en) | 2018-07-25 | 2022-06-16 | Modernatx, Inc. | Mrna based enzyme replacement therapy combined with a pharmacological chaperone for the treatment of lysosomal storage disorders |
| US12594268B2 (en) | 2018-08-20 | 2026-04-07 | Amicus Therapeutics, Inc. | Methods of treating Fabry disease in patients having a mutation in the GLA gene |
| US11612619B2 (en) | 2018-11-01 | 2023-03-28 | National Institute Of Health (Nih), U.S. Dept. Of Health And Human Services (Dhhs), U.S. Government | Compostions and methods for enabling cholesterol catabolism in human cells |
| EP3884383B1 (en) * | 2018-12-21 | 2025-04-16 | Shenzhen Yinwang Intelligent Technologies Co., Ltd. | Data deterministic deliverable communication technology based on qos as a service |
| WO2020168294A1 (en) * | 2019-02-15 | 2020-08-20 | Lysosomal And Rare Disorders Research And Treatment Center, Llc | Methods and compositions for treating lysosomal storage disorders: ambroxol as treatment agent for mucopolysaccharidoses iii (sanfilippo syndrome) |
| EP3996696A1 (en) * | 2019-07-09 | 2022-05-18 | Genethon | Treatment of glycogen storage disease (gsd) |
| KR20220044560A (ko) | 2019-08-07 | 2022-04-08 | 아미쿠스 세라퓨틱스, 인코포레이티드 | Gla 유전자에 돌연변이를 갖는 환자에서 파브리 질병을 치료하는 방법 |
| US12544402B2 (en) | 2020-02-28 | 2026-02-10 | Repair Biotechnologies, Inc. | Targeted expression of microbial cholesterol catalysis genes reduces excess lipid |
| CN112773779B (zh) * | 2021-02-04 | 2022-08-16 | 上海交通大学医学院附属新华医院 | 氨溴索、千金藤和汉防已在治疗酸性鞘磷脂酶缺乏症中的应用 |
| CN114644572B (zh) * | 2022-03-22 | 2023-03-28 | 华南农业大学 | 一种溴己新半抗原、人工抗原、抗体及其制备方法和应用 |
| KR20260002803A (ko) * | 2023-05-02 | 2026-01-06 | 지위, 엘엘씨 | 치료적 사용을 위한 암브록솔의 변형된 형태 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19933148A1 (de) | 1999-07-20 | 2001-01-25 | Boehringer Ingelheim Int | Ambroxolhaltige Lutschtablette |
| EP2857036B1 (en) * | 2003-01-31 | 2016-12-21 | Mount Sinai School of Medicine of New York University | Combination therapy for treating protein deficiency disorders |
| PL2533050T6 (pl) * | 2006-05-16 | 2016-05-31 | Amicus Therapeutics Inc | Możliwości leczenia choroby Fabry'ego |
| JP5337405B2 (ja) * | 2007-09-17 | 2013-11-06 | ザ・ホスピタル・フォー・シック・チルドレン | ゴーシェ病の治療方法 |
| CA2718182A1 (en) * | 2008-03-12 | 2009-09-17 | Amicus Therapeutics, Inc. | Treatment of pompe disease with specific pharmacological chaperones and monitoring treatment using surrogate markers |
| EP2353403B1 (de) * | 2010-02-01 | 2012-07-11 | Symrise AG | Verwendung von 1-(2,4-Dihydroxy-phenyl)-3-(3-hydroxy-4-methoxy-phenyl)-propan-1-on |
-
2012
- 2012-12-21 KR KR1020147019849A patent/KR102076585B1/ko not_active Expired - Fee Related
- 2012-12-21 US US14/367,835 patent/US20150258081A1/en not_active Abandoned
- 2012-12-21 CA CA2860085A patent/CA2860085A1/en not_active Abandoned
- 2012-12-21 EP EP12815644.5A patent/EP2793872B1/en not_active Not-in-force
- 2012-12-21 AU AU2012359165A patent/AU2012359165A1/en not_active Abandoned
- 2012-12-21 ES ES12815644T patent/ES2864774T3/es active Active
- 2012-12-21 JP JP2014547767A patent/JP6320931B2/ja not_active Expired - Fee Related
- 2012-12-21 WO PCT/EP2012/005363 patent/WO2013091897A1/en not_active Ceased
- 2012-12-21 BR BR112014014808A patent/BR112014014808A2/pt not_active Application Discontinuation
-
2014
- 2014-06-16 IL IL233173A patent/IL233173B/en active IP Right Grant
-
2017
- 2017-12-22 AU AU2017279780A patent/AU2017279780B2/en not_active Ceased
- 2017-12-26 JP JP2017248953A patent/JP2018076353A/ja active Pending
-
2021
- 2021-04-05 US US17/222,254 patent/US20210228560A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20210228560A1 (en) | 2021-07-29 |
| EP2793872B1 (en) | 2021-03-10 |
| AU2017279780A1 (en) | 2018-01-25 |
| ES2864774T3 (es) | 2021-10-14 |
| IL233173A0 (en) | 2014-07-31 |
| KR20140107481A (ko) | 2014-09-04 |
| AU2017279780B2 (en) | 2019-10-03 |
| EP2793872A1 (en) | 2014-10-29 |
| KR102076585B1 (ko) | 2020-02-12 |
| WO2013091897A8 (en) | 2014-10-09 |
| BR112014014808A2 (pt) | 2018-09-25 |
| JP2015502964A (ja) | 2015-01-29 |
| IL233173B (en) | 2020-10-29 |
| CA2860085A1 (en) | 2013-06-27 |
| JP2018076353A (ja) | 2018-05-17 |
| JP6320931B2 (ja) | 2018-05-09 |
| WO2013091897A1 (en) | 2013-06-27 |
| US20150258081A1 (en) | 2015-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2017279780B2 (en) | Combination of a compound having the ability to rearrange a lysosomal enzyme and ambroxol and/or a derivative of ambroxol | |
| Boyd et al. | Pharmacological chaperones as therapeutics for lysosomal storage diseases | |
| Mohamed et al. | Pharmaceutical chaperones and proteostasis regulators in the therapy of lysosomal storage disorders: current perspective and future promises | |
| US20150044193A1 (en) | COMPOSITIONS AND METHODS FOR THE TREATMENT OF ALTERED a-SYNUCLEIN FUNCTION | |
| US11571407B2 (en) | Bicalutamide analogs or (S)-bicalutamide as exocytosis activating compounds for use in the treatment of a lysosomal storage disorder or glycogenosis | |
| Pastores et al. | Neuropathic lysosomal storage disorders | |
| US20100317690A1 (en) | Treatment of protein folding disorders | |
| KR102412724B1 (ko) | 리소좀 축적 질환과 관련된 약제 조성물 및 용도 | |
| M Wrodnigg et al. | The two faces of iminoalditols: powerful inhibitors trigger glycosidase activation | |
| RU2750154C2 (ru) | Аримокломол для лечения ассоциированных с глюкоцереброзидазой нарушений | |
| US20180326021A1 (en) | Methods and Compositions for the Treatment of Cytoplasmic Glycogen Storage Disorders | |
| Pradhan et al. | Recent therapeutic advancements for Gaucher disease | |
| HK1243643A1 (zh) | 用於治疗和/或预防脑淀粉样变性的给药方案 | |
| Santra et al. | Lysosomal disorders | |
| WO2024074723A1 (en) | Palatable liquid solution containing high concentration of miglustat | |
| US20210179575A1 (en) | Use of pharmacological chaperones for the treatment of lysosomal storage diseases | |
| Tanpaiboon | Lysosomal storage disorders | |
| Valayannopoulos | Pediatric Neurology Part III: Chapter 190. Enzyme replacement therapy and substrate reduction therapy in lysosomal storage disorders with neurological expression | |
| Amiri | Institute of Physiological Chemistry | |
| Pastores et al. | Enzyme Replacement and Other Therapies for the Lysosomal Storage Disorders | |
| Tanpaiboona | Practical management of lysosomal storage | |
| HK1226945B (zh) | 用於在溶酶体贮积症或糖原贮积病的治疗中使用的作为胞吐作用活化化合物的比卡鲁胺类似物或(s)-比卡鲁胺 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE NAME OF THE INVENTOR TO READ LUKAS, JAN; PEWS-DAVTYAN, ANAHIT; BELLER, MATTHIAS AND ROLFS, ARNDT |
|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE NAME OF THE INVENTOR TO READ LUKAS, JAN; PEWS-DAVTYAN, ANAHIT; BELLER, MATTHIAS; ROLFS, ARNDT AND SHARIF, MUHAMMAD |
|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |